Vitamin D supplementation may lower BP in overweight elderly: Study

Vitamin D supplementation may lower BP in overweight elderly suggests a study published in the Journal of the Endocrine Society.

Supplementation with vitamin D and calcium can reduce systolic and diastolic blood pressure in older individuals with overweight, particularly in those with a body mass index (BMI) > 30 and those diagnosed with hypertension. Large cohort data have provided epidemiologic evidence linking vitamin D deficiency to a higher risk for cardiovascular disorders, including hypertension; however, evidence on the beneficial effects of vitamin D supplementation on blood pressure outcomes remains inconclusive. A post hoc analysis of a randomized controlled trial was conducted to investigate the effect of two doses of cholecalciferol (vitamin D3) on blood pressure in individuals aged 65 years or older with a BMI > 25 and serum vitamin D levels of 10-30 ng/mL. A total of 221 participants were recruited through outpatient departments, clinics, and advertisements in the greater Beirut area and received calcium supplementation in combination with either a low dose (600 IU/d, as recommended by the Institute of Medicine [IOM]) or a high dose (3750 IU/d) of vitamin D3. Blood pressure measurements were taken at baseline, 6 months, and 12 months using a SureSigns VS3 monitor. Participants were also stratified by BMI and hypertension status to assess the effects of vitamin D and calcium on blood pressure. Systolic and diastolic blood pressures were significantly reduced with vitamin D supplementation in the overall cohort (mean difference, 3.5 and 2.8 mm Hg, respectively; P = .005 and P = .002, respectively), with the effect more prominent in those in the high-dose vitamin D group. Participants with a BMI > 30 experienced reductions in both systolic and diastolic blood pressures in the overall cohort (P < .0001 and P = .01, respectively); although the systolic blood pressure was significantly reduced with both high- and low-dose vitamin D, the diastolic blood pressure decreased in the high-dose group only. Patients with hypertension benefited from all doses of vitamin D, regardless of the BMI. Systolic blood pressure at 6 and 12 months was significantly predicted by BMI and baseline systolic blood pressure measurements, although not by the dose of vitamin D received.

“The study found vitamin D supplementation may decrease blood pressure in specific subgroups such as older people, people with obesity, and possibly those with low vitamin D levels,” said study author, Ghada El-Hajj Fuleihan, MD, MPH, of the American University of Beirut Medical Center in Beirut, Lebanon, in a news release. “High vitamin D doses compared to the IOM’s recommended daily dose did not provide additional health benefits.”

Reference:

Maya Rahme, Laila Al-Shaar, Hani Tamim, Ghada El-Hajj Fuleihan, Blood Pressure Decreases in Overweight Elderly Individuals on Vitamin D: A Randomized Trial, Journal of the Endocrine Society, Volume 8, Issue 12, December 2024, bvae168, https://doi.org/10.1210/jendso/bvae168

Keywords:

Vitamin D, supplementation, lower BP, overweight, elderly, study, Journal of the Endocrine Society, Maya Rahme, Laila Al-Shaar, Hani Tamim, Ghada El-Hajj Fuleihan, Blood Pressure

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Chemotherapy during pregnancy associated with increased morbidity and mortality among infants, reveals study

Chemotherapy during pregnancy is associated with increased morbidity and mortality among infants, reveals study published in the Journal of the National Cancer Institute.

Administration of chemotherapy during pregnancy is often delayed, while preterm delivery is common. If in utero exposure to chemotherapy is associated with adverse pediatric outcomes, it is unknown whether that relationship is directly attributable to the chemotherapy or is mediated by preterm birth. Cases were identified from Canadian cancer registries and administrative data in Alberta, British Columbia, and Ontario, 2003-2017, with follow-up until 2018. The primary exposure was receipt of chemotherapy during pregnancy. Severe neonatal morbidity and mortality (SNM-M), neurodevelopmental disorders and disabilities (NDDs) and pediatric complex chronic conditions (PCCC) reflected short- and long-term pediatric outcomes. Modified Poisson and Cox proportional hazard regression models generated adjusted risk ratios (RR) and hazard ratios (HR), respectively. The influence of preterm birth on the association between exposure to chemotherapy in pregnancy and each study outcome was explored using mediation analysis. Results: Of the 1150 incident cases of cancer during pregnancy, 142 (12.3%) received chemotherapy during pregnancy. Exposure to chemotherapy in pregnancy was associated with a higher risk of SNM-M (RR 1.67, 95% CI: 1.13-2.46), but not NDD (HR 0.93, 95% CI: 0.71-1.22) or PCCC (HR 0.96, 95% CI: 0.80-1.16). Preterm birth <34 and <37 weeks mediated 75.8% and 100% of the observed association between chemotherapy and SNM-M, respectively. Most children born to people with cancer during pregnancy appear to have favourable long-term outcomes, even following exposure to chemotherapy in pregnancy. However, preterm birth is quite common, and may contribute to increased rates of adverse neonatal outcomes.

Reference:

Amy Metcalfe, Zoe F Cairncross, Carly A McMorris, Christine M Friedenreich, Gregg Nelson, Parveen Bhatti, Deshayne B Fell, Sarka Lisonkova, Khokan C Sikdar, Lorraine Shack, Joel G Ray, Cancer chemotherapy in pregnancy and adverse pediatric outcomes: a population-based cohort study, JNCI: Journal of the National Cancer Institute, 2024;, djae273, https://doi.org/10.1093/jnci/djae273

Keywords:

Chemotherapy, during, pregnancy, associated, increased, morbidity, mortality, among, infants, reveals, Study , Amy Metcalfe, Zoe F Cairncross, Carly A McMorris, Christine M Friedenreich, Gregg Nelson, Parveen Bhatti, Deshayne B Fell, Sarka Lisonkova, Khokan C Sikdar, Lorraine Shack, Joel G Ray, Cancer, Journal of the National Cancer Institute, Cancer, oncology, pregnancy, toxicity, neonate, pediatric, mediation analysis, risk

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High-dose IV vitamin C plus chemotherapy doubles survival in advanced pancreatic cancer: Study

Results from a randomized phase 2 clinical trial show that adding high-dose, intravenous (IV) vitamin C to chemotherapy doubles the overall survival of patients with late-stage metastatic pancreatic cancer from eight months to 16 months.

“This is a deadly disease with very poor outcomes for patients. The median survival is eight months with treatment, probably less without treatment, and the five-year survival is tiny,” says Joe Cullen, MD, University of Iowa professor of surgery, and radiation oncology, and senior author of the study. “When we started the trial, we thought it would be a success if we got to 12 months survival, but we doubled overall survival to 16 months. The results were so strong in showing the benefit of this therapy for patient survival that we were able to stop the trial early.”

The findings, published in the November issue of Redox Biology, mark another success for high-dose, intravenous vitamin C, which has overcome many hurdles in the almost 20 years UI researchers have persevered to demonstrate its benefit for cancer patients.

“We’ve had ups and downs, of course, but this is a culmination of a lot of people’s hard work,” says Cullen, who also is a member of UI Health Care Holden Comprehensive Cancer Center. “It’s really a positive thing for patients and for the University of Iowa.”

Increased survival, improved quality of life

In the study, 34 patients with stage 4 metastatic pancreatic cancer were randomized to receive either standard chemotherapy (gemcitabine and nab-paclitaxel), or the chemotherapy plus infusions of high-dose vitamin C. The results showed that average overall survival was 16 months for the patients receiving the chemotherapy plus vitamin C, compared to eight months for the patients getting just chemotherapy. In addition, progression-free survival was extended from four months to six months.

“Not only does it increase overall survival, but the patients seem to feel better with the treatment,” Cullen says. “They have less side effects, and appear to be able to tolerate more treatment, and we’ve seen that in other trials, too.”

The new study is not the only evidence of the benefit of including IV vitamin C as part of cancer treatment. Earlier this year, the results of another UI phase 2 clinical trial in patients with glioblastoma, a deadly form of brain cancer, were published. That study also showed a significant increase in survival when high-dose, IV vitamin C was added to standard of care chemotherapy and radiation. Cullen was also part of that trial along with his colleague Bryan Allen, MD, PhD, UI professor and head of radiation oncology.

A third phase 2 trial in non-small cell lung cancer is still underway, with results expected within the year. All three trials were funded by a grant from the National Cancer Institute (NCI).

“This NCI funding was incredibly important for us to conduct these phase 2 trials and obtain these really encouraging results. Our aim is to show that adding high-dose, IV vitamin C, which is very inexpensive and very well tolerated, can improve treatment for these cancers that are among the deadliest affecting the U.S. population,” Cullen adds.

A long journey to clinical trials

Cullen, Allen, and their colleagues at UI Health Care have been researching the anti-cancer effect of high-dose, IV vitamin C for decades. Their work revealed a critical difference between vitamin C given intravenously and vitamin C taken orally. Giving vitamin C through an IV produces very high levels in the blood, which cannot be achieved with oral delivery. These high concentrations result in unique chemical reactions within cancer cells that render the cells more vulnerable to chemo- and radiation therapies.

Cullen notes that despite skepticism towards vitamin C as a cancer therapy, the results he and his colleagues have obtained, from basic science findings to understand the biological mechanisms at work, through the various clinical trials, have been highly encouraging and robust.

“Through every step of the process, it continued to improve. We did it in cells, it worked great. We did it in mice, it worked great. Then our phase one trials looked very promising. So, the progression has just been phenomenal, really,” Cullen says. “For example, in one of our phase 1 trials for pancreatic cancer, where we combine high-dose IV vitamin C with radiation, we still have three long-term survivors. They’re out nine years at this point, which is far beyond the typical survival range.” 

Reference:

Kellie L. Bodeker, Brian J. Smith, Daniel J. Berg, Chandrikha Chandrasekharan, Saima Sharif, Naomi Fei, Sandy Vollstedt, Heather Brown, Meghan Chandler, Amanda Lorack, Stacy McMichael, Jared Wulfekuhle, Brett A. Wagner, Garry R. Buettner, Bryan G. Allen, Joseph M. Caster, Barbara Dion, Mandana Kamgar, John M. Buatti, Joseph J. Cullen,A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer, Redox Biology, https://doi.org/10.1016/j.redox.2024.103375.

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Shorter Incontinence Slings Show Inferior Outcomes but Fewer Complications, Study Finds

Norway: A recent study has raised important questions about the effectiveness and safety of shorter slings used to treat urinary incontinence, a common condition affecting many individuals, particularly women. The study compared shorter sling procedures, designed to treat stress urinary incontinence (SUI), with longer sling techniques, focusing on continence outcomes and safety profiles over 6-12 months.

The findings, published in the International Urogynecology Journal revealed that shorter slings lead to worse continence outcomes, both subjectively and objectively, over 6-12 months, but are associated with fewer complications overall, except for longer-lasting postoperative pain.

Traditional slings, such as tension-free vaginal tape (TVT) and tension-free vaginal tape obturator inside-out (TVT-O), are known for their reliable continence outcomes but can lead to serious complications. To address this, Kjersti Rimstad, Faculty of Medicine, University of Oslo, Oslo, Norway, and colleagues aimed to assess whether slings with less synthetic material, namely Ajust and TVT-O Abbrevo (TVT-A), have similar failure and complication rates over 6 to 12 months, including the risk of prolonged postoperative pain, when compared to traditional slings.

For this purpose, the researchers conducted a registry study using data from the Norwegian Female Incontinence Registry (NFIR), which included 611 patients who received Ajust, 2,772 who received TVT-O Abbrevo (TVT-A), and 18,612 who had traditional slings. The study utilized preoperative, surgical, and 6–12-month follow-up data collected between 2009 and 2021.

Objective failure was defined as ≥1 g of leakage on a standardized cough-jump stress test, while subjective failure was defined as a stress index score ≥3 on a validated questionnaire. Prolonged postoperative pain was defined as pain lasting more than 3 months.

The following were the key findings of the study:

  • At the 6–12 month follow-up, the groups showed significant differences.
  • Objective failure rates: Ajust 15.4%, TVT-A 13.5%, traditional slings 7.3%.
  • Subjective failure rates: Ajust 23.4%, TVT-A 23.8%, traditional slings 18.8%.
  • Shorter slings had fewer overall complications: Ajust 4.9%, TVT-A 6.5%, traditional slings 9.3%.
  • Shorter slings did not have less prolonged postoperative pain: TVT-A 1.4%, Ajust 0.8%, traditional slings 0.7%.
  • All findings remained significant after adjusting for baseline differences.

The findings showed that all types of slings investigated showed good continence outcomes, both subjectively and objectively, with low failure rates after 6–12 months. While the shorter slings demonstrated slightly higher failure rates, the differences were minimal and unlikely to have a significant clinical impact.

Despite the slightly reduced effectiveness of shorter slings, they appeared to result in fewer overall complications. However, the Ajust™ sling was associated with higher rates of new-onset urgency incontinence, and the TVT-A sling had higher rates of prolonged postoperative pain. When comparing the two traditional slings, the TVT had the highest complication rate, while the TVT-O was more comparable to the shorter slings concerning complications.

“The study suggests that there is no definitive “best” sling for surgery, and the choice between a traditional or shorter sling should be based on careful discussion between the patient and doctor, considering both effectiveness and potential risks,” the researchers concluded. “The findings also highlight that the incidence of prolonged postoperative pain is low across all slings, a point that should be communicated to health authorities given ongoing concerns about the future use of synthetic slings for stress urinary incontinence. Further studies are needed to better understand the long-term outcomes and rates of postoperative pain associated with different sling types.”

Reference:

Rimstad, K., Oversand, S.H., Engh, M.E. et al. Effectiveness and Safety of Shorter Incontinence Slings. Int Urogynecol J (2024). https://doi.org/10.1007/s00192-024-05971-5

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Systemic dexamethasone proven treatment for bronchopulmonary dysplasia but role for hydrocortisone uncertain: JAMA

Researchers have discovered that dexamethasone can significantly increase survival free of cerebral palsy in preterm infants at high risk of bronchopulmonary dysplasia (BPD) but may even harm babies with a lower risk of BPD. This underlines that systemic corticosteroid treatments need to be customised according to the individual level of BPD risk in neonatal care. A recent study was conducted by Lex W. and colleagues published in JAMA Pediatrics.

The most frequent complication in former preterm infants is BPD, with later outcomes often severe. In recent years, systemic postnatal corticosteroids, including dexamethasone and hydrocortisone, have been extensively administered to prevent BPD. The objective of this study was to elucidate whether the type of corticosteroid used and the timing of treatment significantly affect survival without cerebral palsy in preterm infants.

This comparative effectiveness study reviewed 26 randomized clinical trials that supported 3,700 infants born preterm and at BPD risk. The studies were conducted across 10 countries between 1989 and 2022 and measured outcomes such as the incidence of BPD, survival rates, and cerebral palsy at diagnosis. The interventions were systemic dexamethasone and hydrocortisone; nearly half of the studies began treatment within the first week of life.

BPD Risk and Treatment Outcomes:

  • Dexamethasone showed improved survival free of cerebral palsy in infants with a BPD risk greater than 70%.

  • Harmful effects were observed in infants with a BPD risk lower than 30%.

  • For every 10% point increase in BPD risk, dexamethasone improved survival rates without cerebral palsy by 3.74% (95% CI: 1.54-5.93%; p= 0.002).

Corticosteroid Comparison:

  • 69% of studies focused on dexamethasone, while 31% analyzed hydrocortisone.

  • Evidence for the benefit of hydrocortisone was weaker, with significant effects only in neonates at 30% or less risk for BPD.

Timing of Treatment:

  • 46% of studies started corticosteroid therapy in the first week after birth.

  • There was no strong evidence that differences in timing affected the outcomes of dexamethasone (interaction coefficient: 0.13; 95% CI: −0.04 to 0.30; p =0.14).

Dexamethasone reduces the risk of subsequent cerebral palsy but increases mortality in high-risk preterm infants without cerebral palsy, a fact for which it should not be used in low-risk patients due to the potential for harm. The studies highlight the requirement for stratifying risks before utilizing corticosteroids in neonates.

Reference:

Doyle, L. W., Mainzer, R., & Cheong, J. L. Y. (2024). Systemic postnatal corticosteroids, bronchopulmonary dysplasia, and survival free of cerebral palsy. JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2024.4575

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E-Cigarette Residue Exposure in Utero Shows Lasting Effects on Immune Response

Results from a new animal study found that maternal exposure to e-cigarette residues, with or without nicotine, affected offspring’s immune response later in life. The study findings are published in the American Journal of Physiology-Lung Cellular and Molecular Physiology. The study has been chosen as an APSselect for November.

When e-cigarettes are used inside a building or vehicle, the vapor condenses on surfaces forming a thick oily layer. Despite growing evidence that direct and second-hand e-cigarette exposure is harmful, less is known about the potential effects of exposure to these vaping residues—known as third-hand exposure.

To find out how maternal third-hand e-cigarette exposure might affect a developing fetus, researchers conducted an experiment examining how this exposure in pregnant mice affects immune response and susceptibility to infections in their offspring later in life.

The researchers mimicked third-hand exposure by using low or high-power e-cigarette settings to deposit e-vapor residues with and without nicotine on to towels, which were changed daily. Mice were exposed to these towels or towels with no e-cigarette residue before, during and after pregnancy.

Once the offspring grew to adulthood, the researchers assessed various markers of immune system functioning. Some of the male adult offspring were also infected with mouse-adapted influenza A virus, and lung and bone marrow immune cell responses were assessed seven days after infection.

The researchers found that maternal third-hand exposure to low- or high-power e-vapor in the presence or absence of nicotine was associated with changes in both the innate and adaptive immune cell responses in offspring. Innate immune cells provide immediate, non-specific defense against pathogens while adaptive immune cells like B and T cells develop a specific and lasting response to specific pathogens.

The flu-infected offspring from the nicotine-exposed groups showed fewer lung alveolar macrophages, cells that play a critical role in the immune response to respiratory infections. These offspring also had more pronounced increases in neutrophils in the bone marrow, which could potentially hinder recovery from infections. Importantly, the e-vapor exposure led to lower activation of the CD4+ T cells and CD8+ T cells in the lungs of the flu-infected offspring, which could potentially compromise the ability to mount an effective immune response.

The researchers said that the study “shows that maternal third-hand exposure to e-vapor, irrespective of the presence of nicotine, exerts long-lasting, potentially detrimental, effects on the immune response of offspring in later life.”

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Induction therapy with infliximab effective against severe Behçet’s syndrome

A recent groundbreaking phase 2 trial compared the induction therapies for severe Behçet’s syndrome revealed that infliximab is both effective and safe than cyclophosphamide. This randomized controlled trial was conducted between May 2018 and April 2021 focused on patients with major vascular and central nervous system involvement who were particularly a high-risk group within Behçet’s disease spectrum.

The study included a total of 52 patients who met the criteria for Behçet’s syndrome of International Study Group. The participants were randomly assigned to receive either intravenous infliximab (5 mg/kg at weeks 0, 2, 6, 12, and 18) or cyclophosphamide (0.7 g/m² at weeks 0, 4, 8, 12, 16, and 20, with a maximum dose of 1.2 g per infusion). All participants were administered a uniform glucocorticoid regimen throughout the trial.

Infliximab demonstrated a significantly higher rate of complete response which was defined as clinical, biological, and radiological remission coupled with a prednisone dose ≤0.1 mg/kg daily by week 22. Also, 22 out of 27 patients (81%) treated with infliximab achieved complete response when compared to 14 out of 25 patients (56%) in the cyclophosphamide group. The estimated difference was 29.8 percentage points, with a 95% credible interval of 6.6 to 51.7. The posterior probability that at least 70% of infliximab-treated individuals would achieve complete response was 97.4%, while the probability of cyclophosphamide stood at only 6.0%. 

Infliximab also demonstrated a more favorable safety profile. Adverse events were reported in 29.6% (8 out of 27) of patients in the infliximab group compared with 64% (16 out of 25) in the cyclophosphamide group. This resulted in an estimated difference of −32.3 percentage points, with a 95% credible interval ranging from −55.2 to −6.6. The rate of serious adverse events was comparable between the two groups, recorded at 15% for infliximab and 12% for cyclophosphamide.

These findings underline the potential of infliximab as a superior induction therapy for patients with severe forms of Behçet’s syndrome, particularly those with vascular or neurological complications. The higher efficacy rate and fewer adverse events suggest that infliximab could be a preferable option over the traditionally used cyclophosphamide, which had a higher burden of side effects. Overall, the study provides strong evidence to favor infliximab as a first-line treatment for severe Behçet’s syndrome.

Source:

Saadoun, D., Maalouf, G., Vieira, M., Trad, S., Lazaro, E., Sacre, K., Plessier, A., Sené, T., Koné-Paut, I., Noel, N., Mekinian, A., Lambert, M., Ribeiro, E., Mirault, T., Mele, N., Dellal, A., Fain, O., Melki, I., Chiche, L., … Cacoub, P. (2024). Infliximab versus Cyclophosphamide for Severe Behçet’s Syndrome. In NEJM Evidence (Vol. 3, Issue 11). Massachusetts Medical Society. https://doi.org/10.1056/evidoa2300354

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Zinc deficiency promotes Acinetobacter lung infection, suggests study

Dietary zinc deficiency promotes lung infection by Acinetobacter baumannii bacteria – a leading cause of ventilator-associated pneumonia, according to a new study published Nov. 15 in the journal Nature Microbiology.

A Vanderbilt University Medical Center-led team of researchers discovered an unexpected link between the pro-inflammatory cytokine interleukin-13 (IL-13) and A. baumannii lung infection, and they demonstrated that blocking IL-13 prevented infection-associated death in an animal model.

The findings suggest that anti-IL-13 antibodies, which are FDA-approved for use in humans, may protect against bacterial pneumonia in patients with zinc deficiency.

“To our knowledge, this is the first study showing that neutralization of IL-13 could prevent mortality from a bacterial infection,” said Eric Skaar, PhD, MPH, the Ernest W. Goodpasture Professor of Pathology and director of the Vanderbilt Institute for Infection, Immunology and Inflammation. “This discovery points to the possibility of using anti-IL-13 therapy in patients with zinc deficiency and A. baumannii pneumonia as part of a personalized therapy approach.”

Nearly 20% of the world’s population is at risk for zinc deficiency, which can impair immune function and is a major risk factor for pneumonia. The World Health Organization considers zinc deficiency a leading contributor to disease and death.

Patients at risk for zinc deficiency, particularly critically ill and elderly patients, are also at risk for A. baumannii infection. Patients in health care settings have the highest risk for infection, especially those who are on ventilators, have devices such as catheters, are in intensive care units, or have prolonged hospital stays. A. baumannii is becoming increasingly resistant to antimicrobial treatments, making it a critical public health threat, Skaar said.

To explore whether and how dietary zinc deficiency contributes to A. baumannii pathogenesis, the researchers established a mouse model of dietary zinc deficiency and acute A. baumannii pneumonia. Lauren Palmer, PhD, a former postdoctoral fellow at VUMC who is now assistant professor of Microbiology and Immunology at the University of Illinois, Chicago, led the studies.

The researchers found that zinc-deficient mice had increased A. baumannii bacterial burden in the lungs, spread of bacteria to the spleen, and higher mortality compared to mice with adequate dietary zinc consumption. They showed that the zinc-deficient mice produce more IL-13 during infection and that administration of IL-13 to mice with sufficient zinc promoted spread of A. baumannii to the spleen. Anti-IL-13 antibody treatment protected zinc-deficient mice from A. baumannii-induced death.

The findings add to a growing set of studies showing that certain nutrient deficiencies are associated with IL-13 production and a “type 2” immune response.

“IL-13 may be an important risk factor for health care-associated and opportunistic lung infections, further supporting exploration of IL-13 as a target for treatment,” Skaar noted.

FDA-approved anti-IL-13 antibodies (lebrikizumab and tralokinumab) have been extensively investigated as potential therapies for uncontrolled severe asthma. Although they were not found to be effective for that indication, the clinical trials demonstrated their safety. 

References: Lauren D. Palmer, Kacie A. Traina, Lillian J. Juttukonda, Zachery R. Lonergan, Dziedzom A. Bansah, Xiaomei Ren, John H. Geary, Christopher Pinelli, Kelli L. Boyd, Tzushan S. Yang & Eric P. Skaar Nature Microbiology (2024)Cite this article Metrics

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Early Intratracheal Budesonide Treatment Has Minimal Effect on BPD-Free Survival in Preterm Infants: PLUSS Trial

Australia: In extremely preterm infants treated with surfactant for respiratory distress syndrome, early administration of intratracheal budesonide may have minimal to no impact on survival without bronchopulmonary dysplasia (BPD), PLUSS trial has shown. The findings were published online in the Journal of the American Medical Association (JAMA). 

The clinical trial explored whether combining intratracheal budesonide, a steroid, with surfactant therapy can improve outcomes for extremely preterm infants facing respiratory distress syndrome (RDS). The study, known as the PLUSS (Prevention of Lung Injury with Surfactant and Steroid) trial, specifically targeted infants born at 23 to 28 weeks of gestation—one of the most vulnerable groups for developing bronchopulmonary dysplasia, a chronic lung condition that often arises in premature babies due to prolonged ventilation and oxygen therapy.

Bronchopulmonary dysplasia is a frequent and serious complication in extremely preterm infants born at less than 28 weeks gestation. While systemic corticosteroids reduce the risk of BPD, they may carry potential risks of adverse effects. In contrast, administering corticosteroids directly into the lungs could offer a more targeted approach with fewer side effects. With this in mind, Brett J. Manley, Newborn Research, The Royal Women’s Hospital, Melbourne, Victoria, Australia, and colleagues aimed to assess the effectiveness of early intratracheal corticosteroid treatment in improving survival rates free of BPD in extremely preterm infants.

For this purpose, the researchers conducted a double-blind, randomized clinical trial across 21 neonatal units in four countries (Australia, New Zealand, Canada, and Singapore). The study enrolled infants born at less than 28 weeks gestation, aged under 48 hours, and requiring respiratory support, including those treated with surfactant. From January 2018 to March 2023, infants were randomly assigned to receive either intratracheal budesonide mixed with surfactant or surfactant alone.

The primary outcome was survival free of bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age, and 15 secondary and safety outcomes were assessed.

The study led to the following findings:

  • The primary analysis included 1,059 infants: 524 in the budesonide and surfactant group and 535 in the surfactant-only group.
  • The mean gestational age was 25.6 weeks, and the mean birth weight was 775 g; 55.3% of infants were male.
  • Survival free of BPD occurred in 25.6% of infants in the budesonide and surfactant group, compared to 22.6% in the surfactant-only group (adjusted risk difference, 2.7%).
  • At 36 weeks postmenstrual age, 83.2% of infants in the budesonide and surfactant group and 80.6% in the surfactant-only group were alive.
  • Among those alive, 69.3% in the budesonide and surfactant group and 71.9% in the surfactant-only group were diagnosed with BPD.

The findings revealed that in extremely preterm infants with respiratory distress syndrome who received surfactant, early intratracheal budesonide may not significantly affect the chances of surviving without bronchopulmonary dysplasia at 36 weeks postmenstrual age.

“Long-term results from this trial at 2 years, along with findings from similar large studies, will be crucial to better understand the effectiveness and safety of intratracheal budesonide and its potential role in treatment,” the researchers concluded.

Reference:

Manley BJ, Kamlin COF, Donath SM, et al. Intratracheal Budesonide Mixed With Surfactant for Extremely Preterm Infants: The PLUSS Randomized Clinical Trial. JAMA. Published online November 11, 2024. doi:10.1001/jama.2024.17380

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Hybrid technique effective alternative to bag-mask ventilation to enhance ventilation efficiency, suggests study

Effective bag-mask ventilation (BMV) is crucial for managing the airway and preventing irreversible hypoxia, making it essential for all healthcare providers, including new trainees, to be proficient in efficient BMV techniques. Proper patient positioning, airway patency, and a secure mask seal are vital for successful BMV. Studies have identified various factors, such as edentulous patients, beard presence, advanced age, high BMI, history of snoring, and incorrectly sized masks, as predictors of difficult BMV, which can be addressed by using a two-handed BMV technique with an appropriately fitting mask. Recent randomized controlled study compared the effectiveness of two different bag-mask ventilation (BMV) techniques performed by novice airway providers. One group received BMV using the conventional double-handed CE technique, while the other group used a hybrid technique with the dominant hand in the CE grip and the non-dominant hand on the thenar eminence.

The primary outcome was the 2-minute (24 breaths) mean exhaled tidal volume between the two groups. The secondary outcomes were the number of failed breaths (no exhaled tidal volume) and the comfort level of the airway providers using a 5-point Likert scale.

The study found that the mean exhaled tidal volume was significantly higher in the group using the hybrid technique (476.71 mL) compared to the group using the traditional CE technique (377.51 mL). The mean end-tidal carbon dioxide was also significantly higher in the hybrid technique group (30.42 mmHg) versus the CE technique group (28.83 mmHg). The number of failed breaths was comparable between the two groups, with 4 patients experiencing 2 failed breaths each. The comfort level of the airway providers was also similar, with over 50% finding both techniques very comfortable or comfortable.

Conclusion

The results suggest that the dominant-hand CE and non-dominant-hand thenar eminence hybrid technique provides higher exhaled tidal volumes and end-tidal carbon dioxide levels compared to the traditional CE technique, with similar provider comfort levels. This hybrid technique may be considered an effective alternative BMV method, especially for novice airway providers. The study highlights the potential benefits of combining established BMV techniques to enhance ventilation efficiency, particularly when performed by less experienced clinicians. Further research is warranted to validate these findings and explore the utility of hybrid BMV approaches in various clinical settings.

Key Points

1. The study compared the effectiveness of two different bag-mask ventilation (BMV) techniques – the conventional double-handed CE technique and a hybrid technique using the dominant hand in the CE grip and the non-dominant hand on the thenar eminence.

2. The primary outcome was the 2-minute mean exhaled tidal volume between the two groups, while the secondary outcomes were the number of failed breaths and the comfort level of the airway providers.

3. The results showed that the mean exhaled tidal volume and end-tidal carbon dioxide were significantly higher in the group using the hybrid technique compared to the group using the traditional CE technique.

4. The number of failed breaths was similar between the two groups, with 4 patients experiencing 2 failed breaths each. The comfort level of the airway providers was also comparable, with over 50% finding both techniques very comfortable or comfortable.

5. The study suggests that the dominant-hand CE and non-dominant-hand thenar eminence hybrid technique may be considered an effective alternative BMV method, especially for novice airway providers.

6. The study highlights the potential benefits of combining established BMV techniques to enhance ventilation efficiency, and further research is warranted to validate these findings and explore the utility of hybrid BMV approaches in various clinical settings.

Reference –

Saroye N, Kaur G, Singh U, Grewal A, Khanna A, Nayyar R. Evaluation of efficacy of two bag‑mask ventilation techniques by novice airway providers: Two‑handed CE versus dominant‑hand CE–non‑dominant‑hand thenar eminence techniques – A randomised controlled trial. Indian J Anaesth 2024;68:1010‑5

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